Several research studies have shown that xylitol added to a cariogenic diet may reduce the caries incidence in man. Thus, for example, Wales et al, "The Effect of Xylitol on Plaque Metabolism", Swed. Dent. J., Volume 8, Issue 3, pp. 155-61 (1984) present evidence that Strep mitior and Strep mutans are unable to metabolize xylitol and transfer it to xylitol phosphate. Such article suggests that the accumulation of xylitol phosphate inside cells may poison bacteria and this possibly explains the cariestherapeutic effect of xylitol observed in some laboratories.
However, the incorporation of xylitol into pharmaceutical and/or confectionery products such as gum or tablets has been difficult due to the physical form of the aqueous crystallized xylitol available.
Thus, traditionally xylitol has been produced by the crystallization of a saturated aqueous solution of xylitol to form single crystals, tetrahedron in shape, of relatively uniform size. These crystals are grown in solution, separated from solution by centrifuging, drying the crystals and then grinding them into a powder. Thus, for example, Kirk-Othmer, Encyclopedia of Chemical Technology, Third Ed., (1978), John Wiley & Sons, indicate (at Vol. I, page 766) that "Xylose is obtained from sulfite liquors, particularly from hardwoods, such as birch, by methanol extraction of concentrates or dried sulfite lyes, ultrafiltration and reverse osmosis, ion exchange, ion exclusion, or combinations of these treatments . . . hydrogenation of xylose to xylitol is carried out in aqueous solution, usually at basic pH, with Raney nickel catalyst at a loading of 2%, at 125.degree. C. and 3.5 MPa (515 psi)". An alternative aqueous crystallization process is described in U.S. Pat. No. 3,985,515 to Jaffe et al.
Xylitol produced in this fashion is typically very moisture sensitive and is thus prone to caking, making it difficult to use such product after periods of storage due to the clumping that typically occurs. When xylitol powder is employed in sucrose free chewing gum, where it is used as part of the sweetner/bulking agent as a replacement for sugar, manufacturers may typically bring in xylitol crystallized from solution in bulk, unground form then grind it down themselves, just prior to addition to the gum batch, in order to minimize caking and the problems associated therewith.
Moreover, due to its crystalline structure, i.e., distinct single crystal, definitive form, and very dense nature, when added to gum, aqueous crystallized xylitol does not "dry" the gum out and even with reductions in plasticizer, the gum is typically very soft and difficult to handle/process in gum plants. At the typical use levels of 7-15% (based on total weight), gum containing aqueous crystallized xylitol poses unique handling problems.
A further result of the single crystalline form of aqueous crystallized xylitol is that such structure does not allow for any "copenetration" of the crystals to effect a bond of the crystals; the dense nature of the crystal has very low plastic deformation characteristics or values and the bonding energy of the crystal is low. As a result, it is not possible to make a direct compression tablet from xylitol powder produced from an aqueous crystallization process. Rather, one must first "agglomerate" the xylitol powder by wetting it with water in a high velocity air stream to form an agglomerate, and then drying and sizing the resulting product. Product produced by this process can be used in direct compression applications to make tablets of good hardness and durability. It is an added expense however to have to agglomerate the product from the ground aqueous crystallized xylitol. The added expense plus the "grittiness" that is acquired in the agglomeration process has greatly limited the use of xylitol as an excipient for tablet manufacture.
My copending U.S. patent application Ser. No. 07/441,131 discloses pharmaceutical compositions comprising a sugar alcohol derived from at least one mono- or polysaccharide having dispersed within its crystal matrix particles of at least one pharmaceutically active compound, as well as a method of producing such a uniformly dispersed pharmaceutical composition. It has now been unexpectedly found that when sorbitol is employed as the saccharide derivative and xylitol as the dispersed pharmaceutical active, cocrystallized materials are produced which provide unexpectedly desirable processing activity relative to blends of the crystalline materials alone in the formation of consumables such as tablets, chewing gums, and the like.